Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort

Florian Rader, Artur Oręziak, Lubna Choudhury, Sara Saberi, David Fermin, Matthew T. Wheeler, Theodore P. Abraham, Pablo Garcia-Pavia, Donna R. Zwas, Ahmad Masri, Anjali Owens, Sheila M. Hegde, Tim Seidler, Shawna Fox, Ganesh Balaratnam, Amy J. Sehnert, Iacopo Olivotto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed. Objectives: The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655). Methods: After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms. Results: Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: −35.6 ± 32.6 mm Hg; Valsalva: −45.3 ± 35.9 mm Hg), N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels (median: −480 ng/L; Q1-Q3: −1,104 to −179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events. Conclusions: Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.

Original languageEnglish (US)
Pages (from-to)164-177
Number of pages14
JournalJACC: Heart Failure
Volume12
Issue number1
DOIs
StatePublished - Jan 2024

Keywords

  • LVOT gradient
  • NT-proBNP
  • NYHA functional class
  • efficacy
  • long-term outcomes
  • safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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